Background: 50 years ago humans returned to this region of the world for the first time in hundreds of years. An adventurer wizard claimed this tower, rebuilt it from a shell into a defensible wilderness keep. He lived in it for about 10 years. Then something happened. The top floor (of 4) is blown off, and everyone in the tower at the time (wizard, 6-8 servants and apprentices, 10-12 men-at-arms) all died or vanished.

Since then: adventurers have explored the ruins many times; it is about 30 miles outside the boundaries of the current "settled" region, but in a not-too-dangerous area for young adventurers establishing themselves. Sometimes it is used as a lair by orc tribes, wild animals, owlbears, etc...
but rumor is that there's something strange about the tower; some people have vanished near it, and others report feelings of terror, cold spots and general creepiness.

What happened? What's going on? Is it just monsters? Something hidden? Give me some ideas! They've just finished exploring an undead tomb, so I'd prefer not to reuse that idea.

T'enik the wizard, in his drive for power and knowledge, discovered and tampered with magic beyond his understanding and control. In an attempt to contact mysterious and powerful beings from whom he hoped to wrest the secrets of the universe, he ripped a small tear in the fabric of reality, giving an ancient abomination from the far realms a finger-hold into the adventurers' world and reality.

T'enik himself didn't die, but instead was transformed into a nothic that continues his miserable existence among the basted remains of the top of the tower.

While creatures have used the lower levels tower as hide outs or lairs, none have gone to the top of the tower. Seeping powers of the far realm cause nightmare hallucinations and fear to any who try to explore the top of the tower.

If the party goes to the top of the tower and over comes their fear they will have to fight a hallucinatory nightmare beast. The encounter should be a deadly encounter, but if they prevail, everyone who "died" and all damage disappears. This will free the tower from the negative affects of the far realm for 24 hours. The party can then encounter T'enik and by trading magic or arcane knowledge with him, learn about what happened and that if the tear in the fabric of reality is not fixed, it will create a port through which [insert some elder evil] will enter and unleash untold horrors on the world.

The party will need to get some macguffin and return to undo the damage T'enik has done.

I used an ancient ruined tower for a campaign adventure/camp for the party. The tower, though with holes in the walls and the top layer missing, was still inhabitable and became the party's home base as they explored it. It seems the wizard was trying to build a multidimensional fortress and the tower still had several secrets that led to mini adventures in other parts of the fortress in those other dimensions. The tower existed in each of those other dimensions, mostly intact in most. The dimensions that caused the destruction bled over onto the Prime plane but not all these other planes. The wizard was destroyed by a demon prince who kept his soul as a trophy for the temerity of building in his realm without permission or promise of fealty. The demon prince was unaware that the tower spanned dimensions so does not care that the whole tower was not destroyed, only the parts in his realm mattered to him.

I had something like this in my game, only the whole tower blew up, not just the top floor. Only thing surviving was his dungeon, which sort of reflected his descent into madness

The first floor of the dungeon was devoted to hobbies - art, music, theater. But he wanted to create more than art, he wanted to create life. The second floor was devoted to bringing back the dead, not as undead per se, but more like from Frankenstein and Re-Animator. The third level was vats where he created monsters, the fourth was where he kept some of the monsters, etc.

...as it happened, the wizard was able to "rebuild" the tower due to his extensive amount of warforged-grafts. Well, he and the warforged-animating-spirits had a falling out, and only the warforged parts remain.

Sustaining nourishment from a makeshift solar panel on the destroyed roof.

And causing wanderers to disappear because it needs something to fill the Scream Pit in the dungeon...